CrackCast Show Notes – Jaundice – August 2020 www.canadiem.org/crackcast Chapter 25 - Jaundice EPISODE CONTENT BASED ON ROSEN’S EMERGENCY MEDICINE (9TH ED.) Italicized text is quoted directly from Rosen’s. Key Concepts: 1. Clinical Jaundice is usually not evident until total serum bilirubin rises above 2.5mg/dl (~43µmol/L for our Canadian listeners) 2. Bile metabolism can be altered when there is overproduction of heme products (hemolysis); failure of hepatocyte to take up, conjugate and excrete bilirubin (hepatocellular dysfunction); or obstruction of biliary excretion into the intestine. 3. Unconjugated bilirubin that is not bound to albumin can cross the BBB, causing toxic neurologic effects. 4. New onset painless jaundice is the classic presentation for a pancreatic head neoplasm. 5. Jaundice is first apparent sublingually, in the conjunctiva, and on the hard palate. 6. In cases of unexplained liver injury, a quantitative APAP level may be helpful. 7. If the etiology of the ascites is unknown, getting the serum ascites albumin gradient (SAAG) will aid in determining the cause of the ascites and presence of portal hypertension. 8. US is the preferred initial modality to evaluate whether or not biliary obstruction is present, whereas CT is preferred if malignant obstruction is suspected, or the entire abdomen needs to be evaluated. 9. Elevated direct bilirubin with transaminase elevation is indicative of hepatocellular inflammation or injury. 10. Hyperemesis gravidarum can elevate liver enzymes up to 20 times the normal amount, including mildly elevated bilirubin. 11. Intrahepatic cholestasis of pregnancy is an idiopathic cause of jaundice that occurs in the third trimester. CrackCast Show Notes – Jaundice – August 2020 www.canadiem.org/crackcast Core Questions 1. Explain broad causes of elevated bilirubin (obstructive, hepatocellular, and hemolysis) and the significance of direct vs. indirect hyperbilirubinemia (Fig 25.1) 2. Explain your approach to the history and physical exam in patients with jaundice (Fig 25.2) 3. List 10 causes of jaundice (Table 25.2) 4. Explain your approach to ancillary testing in patients with jaundice. Wisecracks 1. What are the stages of hepatic encephalopathy? 2. What is the triad of acute hepatic failure? 3. What is Charcot’s triad and Reynold’s pentad? 4. What is the “1000s Club” and how do you become a member? R osen’s in Perspective Jaundice is one of those ED complaints that is a bit more rare than some of the standard cases we see every shift. However, there is a wide range of causes for jaundice, and an understanding of pathophysiology is key. We have got you covered here at CRACKCast - the next time you walk into a room and your patient is as yellow as Homer Simpson, you will know exactly what to do! A few points to highlight from those first few Rosen’s paragraphs. Jaundice is clinically evident at 2.5mg/dl or about 43µmol/L, first seen in tissues with relatively high concentrations of albumin (eyes and skin). Remember that there are 3 categories of bilirubin problems - increased production due to hemolysis, hepatocellular dysfunction causing impaired uptake and conjugation, and obstruction pathologies that prevent bilirubin excretion. When it comes to neurotoxicity, unconjugated bili is the one we worry about - this is not bound to albumin, and can cause encephalopathy and kernicterus. CrackCast Show Notes – Jaundice – August 2020 www.canadiem.org/crackcast Core Questions: [ 1] Explain broad causes of elevated bilirubin (obstructive, hepatocellular, and hemolysis) and ​ the significance of direct vs. indirect hyperbilirubinemia (Fig 25.1) Bilirubin is a byproduct of heme breakdown. This is released into its unconjugated form into the circulation and bound to albumin. It is then ​ ​ taken up into the hepatocytes where it is conjugated. Conjugated bilirubin is taken up and ​ ​ stored in the hepatocytes, and then subsequently excreted into the intestine. Direct hyperbilirubinemia = conjugated bilirubin ​ ● Obstructive causes to consider: ​ ○ Choledocolithiasis ○ Intrinsic bile duct disease (cholangitis, stricture, neoplasm, extrinsic compression) ○ Extrinsic compression ● Hepatocellular causes ○ Viral hepatitis ○ Hepatic failure ○ Alcoholic hepatitis ○ Ischemia ○ Toxins ○ Autoimmune hepatitis ○ HELLP syndrome Indirect hyperbilirubinemia = unconjugated bilirubin ​ ● Hematologic causes ○ Hemolysis ○ Hematoma resorption ○ Ineffective erythropoiesis ○ Gilbert’s syndrome See figure 25.1 for more details. [ 2] Explain your approach to the history and physical exam in patients with jaundice (Fig 25.2) ​ CrackCast Show Notes – Jaundice – August 2020 www.canadiem.org/crackcast Figure 25.2: Pivotal points in the assessment of the jaundiced patient. History ● Viral prodrome ● Liver disease ● Alcohol/IVDU ● Biliary surgery ● Fever/abdo pain ● Pregnancy ● Toxic ingestion ● Cancer history ● History of blood products ● Occupational exposure ● CV disease ● Trauma ● Travel history Exam: ● Mental status ● Abdominal tenderness/HSM ● Skin findings - petechiae/purpura, caput medusae, spider angiomata ● Ascites ● Pulsatile mass [ 3] List 10 causes of jaundice (Table 25.2) ​ CrackCast Show Notes – Jaundice – August 2020 www.canadiem.org/crackcast Table 25.2: Jaundice: Differential diagnosis of critical and emergent causes SYSTEM CRITICAL EMERGENT NONEMERGENT Hepatitis of any Hepatitis with cause with normal mental confusion, status, normal vital bleeding, or signs, and no coagulopathy active bleeding Wilson’s disease Primary biliary cirrhosis Autoimmune hepatitis Fulminant hepatic failure; Toxin, Hepatic Virus, Alcohol, Ischemic insult, Liver transplant Reye’s syndrome rejection Infiltrative liver disease Drug induced (isoniazid, phenytoin, acetaminophen, ritonavir, halothane, sulfonamides) Toxin ingestion or exposure CrackCast Show Notes – Jaundice – August 2020 www.canadiem.org/crackcast Bile duct obstruction (stone, Biliary Cholangitis inflammation, stricture, neoplasm) Post-traumatic Sepsis Sarcoidosis hematoma resorption Systemic Total parenteral Heatstroke Amyloidosis nutrition Graft-versus-host disease Right-sided Obstructing AAA congestive heart failure Cardiovascular Veno-occlusive Budd-Chiari syndrome disease Severe congestive heart failure Hemolytic Transfusion reaction Gilbert’s syndrome anemia Massive Physiologic malignant neonatal jaundice infiltration Hematologic-on Inborn error of cologic metabolism Pancreatic head tumor Metastatic disease CrackCast Show Notes – Jaundice – August 2020 www.canadiem.org/crackcast Hyperemesis Preeclampsia or HELLP syndrome gravidarum Reproductive Cholestasis of Acute fatty liver of pregnancy pregnancy [ 4] Explain your approach to ancillary testing in patients with jaundice. ​ Lab considerations: Bilirubin: Conjugated vs. Unconjugated as discussed in previous question Conjugated - think hepatic causes Unconjugated - think hemolytic causes (send LDH, haptoglobin, reticulocyte count, peripheral smear, coombs test) Liver enzymes: ● AST (intracellular, liver, heart, muscle, kidneys, brain, pancreas, lungs, RBC, LBC) ● ALT (specific to Liver) ​ ​ ● ALP (liver, bone, placenta, gut) ● GGT - specific to liver, can help confirm that ALP elevation caused by liver Cholestatic vs. Hepatocellular pattern: Cholestatic enzymes = ALP/GGT/Bili Hepatocellular enzymes = AST/ALT Liver function tests: Albumin INR Imaging - in general, ultrasound is the best place to start assessing for liver/gallbladder/CBD pathology. It can assess for cirrhosis, portal HTN, and ascites as well. CrackCast Show Notes – Jaundice – August 2020 www.canadiem.org/crackcast Acute abdomen/undifferentiated sick patient: CT abdo/pelvis is never a bad idea Wisecracks: [ 1] What are the stages of hepatic encephalopathy? ​ Table 25.1 CLINICAL INTELLECTUAL FUNCTION NEUROMUSCULAR FUNCTION STAGE Normal examination findings, but work Subtle changes in psychometric Subclinical or driving may be impaired testing Impaired attention, irritability, Stage 1 Tremor, incoordination, apraxia depression, or personality changes Drowsiness, behavioral changes, poor Asterixis, slowed or slurred speech, Stage 2 memory, disturbed sleep ataxia Confusion, disorientation, somnolence, Hypoactive reflexes, nystagmus, Stage 3 amnesia clonus, muscular rigidity Dilated pupils and decerebrate Stage 4 Stupor and coma posturing; oculocephalic reflex [ 2] What is the triad of acute hepatic failure? ​ Jaundice, encephalopathy, coagulopathy INR > 1.5 These can be some of the sickest patients in the hospital. When managing acute hepatic failure, think of the the complications of liver failure and go from there CrackCast Show Notes – Jaundice – August 2020 www.canadiem.org/crackcast SCREAM ● Sepsis - fluids/antibiotics/source control. Increased susceptibility to bacterial and fungal ​ infections ● Coagulopathy - vitamin K, FFP/Platelets if actively bleeding or invasive procedures ​ required. GI bleeds can occur if pt has varices. ● Renal Failure - Dialysis if indicated. ​ ○ Hepatorenal syndrome and severe peripheral edema can occur ● Encephalopathy - acute setting - ICP management, lactulose/limited protein intake in ​ hospital. Consider intubating and initiating ICP care for grade ¾ encephalopathy ● Ascites (keep SBP on ddx) ​ ● Metabolic (hypoglycemia, electrolyte imbalance, acidosis) ​ ○ Hypoglycemia - D10 infusion ○ Acidosis - Bicarb infusion ○ Electrolytes - (hyponatremia, hypokalemia, hypophosphatemia) ● Detoxification with NAC if due to acetaminophen ingestion ​ Get your medicine/GI/ICU colleagues on board for these! Transfer to a transplant